TISIDB

Summary
Symbol	CXCL8
Name	chemokine (C-X-C motif) ligand 8
Aliases	SCYB8; LUCT; LECT; MDNCF; TSG-1; IL-8; NAP-1; 3-10C; MONAP; AMCF-I; LYNAP; NAF; b-ENAP; K60; GCP1; neutrophi ......
Chromosomal Location	4q13-q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Secreted.
Domain	PF00048 Small cytokines (intecrine/chemokine)
Function	IL-8 is a chemotactic factor that attracts neutrophils, basophils, and T-cells, but not monocytes. It is also involved in neutrophil activation. It is released from several cell types in response to an inflammatory stimulus. IL-8(6-77) has a 5-10-fold higher activity on neutrophil activation, IL-8(5-77) has increased activity on neutrophil activation and IL-8(7-77) has a higher affinity to receptors CXCR1 and CXCR2 as compared to IL-8(1-77), respectively.

> Gene Ontology [ TOP ]
Biological Process	GO:0001525 angiogenesis GO:0002237 response to molecule of bacterial origin GO:0002274 myeloid leukocyte activation GO:0002685 regulation of leukocyte migration GO:0002687 positive regulation of leukocyte migration GO:0002688 regulation of leukocyte chemotaxis GO:0002690 positive regulation of leukocyte chemotaxis GO:0006898 receptor-mediated endocytosis GO:0006984 ER-nucleus signaling pathway GO:0006986 response to unfolded protein GO:0007050 cell cycle arrest GO:0008277 regulation of G-protein coupled receptor protein signaling pathway GO:0019058 viral life cycle GO:0019079 viral genome replication GO:0019722 calcium-mediated signaling GO:0019932 second-messenger-mediated signaling GO:0030260 entry into host cell GO:0030335 positive regulation of cell migration GO:0030593 neutrophil chemotaxis GO:0030595 leukocyte chemotaxis GO:0030968 endoplasmic reticulum unfolded protein response GO:0031623 receptor internalization GO:0032103 positive regulation of response to external stimulus GO:0032496 response to lipopolysaccharide GO:0034612 response to tumor necrosis factor GO:0034620 cellular response to unfolded protein GO:0034976 response to endoplasmic reticulum stress GO:0035635 entry of bacterium into host cell GO:0035966 response to topologically incorrect protein GO:0035967 cellular response to topologically incorrect protein GO:0036230 granulocyte activation GO:0036499 PERK-mediated unfolded protein response GO:0039692 single stranded viral RNA replication via double stranded DNA intermediate GO:0039694 viral RNA genome replication GO:0039703 RNA replication GO:0040017 positive regulation of locomotion GO:0042119 neutrophil activation GO:0043112 receptor metabolic process GO:0043900 regulation of multi-organism process GO:0043903 regulation of symbiosis, encompassing mutualism through parasitism GO:0044033 multi-organism metabolic process GO:0044344 cellular response to fibroblast growth factor stimulus GO:0044409 entry into host GO:0045069 regulation of viral genome replication GO:0045091 regulation of single stranded viral RNA replication via double stranded DNA intermediate GO:0045744 negative regulation of G-protein coupled receptor protein signaling pathway GO:0045765 regulation of angiogenesis GO:0045766 positive regulation of angiogenesis GO:0045786 negative regulation of cell cycle GO:0048514 blood vessel morphogenesis GO:0048565 digestive tract development GO:0048566 embryonic digestive tract development GO:0048568 embryonic organ development GO:0050792 regulation of viral process GO:0050900 leukocyte migration GO:0050918 positive chemotaxis GO:0050920 regulation of chemotaxis GO:0050921 positive regulation of chemotaxis GO:0050926 regulation of positive chemotaxis GO:0050927 positive regulation of positive chemotaxis GO:0050930 induction of positive chemotaxis GO:0051052 regulation of DNA metabolic process GO:0051272 positive regulation of cellular component movement GO:0051701 interaction with host GO:0051806 entry into cell of other organism involved in symbiotic interaction GO:0051828 entry into other organism involved in symbiotic interaction GO:0055123 digestive system development GO:0060326 cell chemotaxis GO:0070098 chemokine-mediated signaling pathway GO:0070555 response to interleukin-1 GO:0071216 cellular response to biotic stimulus GO:0071219 cellular response to molecule of bacterial origin GO:0071222 cellular response to lipopolysaccharide GO:0071347 cellular response to interleukin-1 GO:0071356 cellular response to tumor necrosis factor GO:0071396 cellular response to lipid GO:0071621 granulocyte chemotaxis GO:0071622 regulation of granulocyte chemotaxis GO:0071624 positive regulation of granulocyte chemotaxis GO:0071774 response to fibroblast growth factor GO:0090022 regulation of neutrophil chemotaxis GO:0090023 positive regulation of neutrophil chemotaxis GO:0097529 myeloid leukocyte migration GO:0097530 granulocyte migration GO:1901342 regulation of vasculature development GO:1902622 regulation of neutrophil migration GO:1902624 positive regulation of neutrophil migration GO:1903900 regulation of viral life cycle GO:1904018 positive regulation of vasculature development GO:1990266 neutrophil migration GO:2000147 positive regulation of cell motility GO:2000535 regulation of entry of bacterium into host cell
Molecular Function	GO:0001664 G-protein coupled receptor binding GO:0005125 cytokine activity GO:0005126 cytokine receptor binding GO:0005153 interleukin-8 receptor binding GO:0008009 chemokine activity GO:0042379 chemokine receptor binding GO:0045236 CXCR chemokine receptor binding
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04060 Cytokine-cytokine receptor interaction hsa04062 Chemokine signaling pathway hsa04064 NF-kappa B signaling pathway hsa04620 Toll-like receptor signaling pathway hsa04621 NOD-like receptor signaling pathway hsa04622 RIG-I-like receptor signaling pathway
Reactome	R-HSA-380994: ATF4 activates genes R-HSA-2559583: Cellular Senescence R-HSA-2262752: Cellular responses to stress R-HSA-380108: Chemokine receptors bind chemokines R-HSA-373076: Class A/1 (Rhodopsin-like receptors) R-HSA-1280215: Cytokine Signaling in Immune system R-HSA-418594: G alpha (i) signalling events R-HSA-388396: GPCR downstream signaling R-HSA-500792: GPCR ligand binding R-HSA-168256: Immune System R-HSA-6783783: Interleukin-10 signaling R-HSA-6785807: Interleukin-4 and 13 signaling R-HSA-392499: Metabolism of proteins R-HSA-381042: PERK regulates gene expression R-HSA-375276: Peptide ligand-binding receptors R-HSA-2559582: Senescence-Associated Secretory Phenotype (SASP) R-HSA-162582: Signal Transduction R-HSA-372790: Signaling by GPCR R-HSA-449147: Signaling by Interleukins R-HSA-381119: Unfolded Protein Response (UPR)

> KEGG and Reactome Pathway

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KEGG

hsa04060 Cytokine-cytokine receptor interaction
hsa04062 Chemokine signaling pathway
hsa04064 NF-kappa B signaling pathway
hsa04620 Toll-like receptor signaling pathway
hsa04621 NOD-like receptor signaling pathway
hsa04622 RIG-I-like receptor signaling pathway

Reactome

R-HSA-380994: ATF4 activates genes
R-HSA-2559583: Cellular Senescence
R-HSA-2262752: Cellular responses to stress
R-HSA-380108: Chemokine receptors bind chemokines
R-HSA-373076: Class A/1 (Rhodopsin-like receptors)
R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-418594: G alpha (i) signalling events
R-HSA-388396: GPCR downstream signaling
R-HSA-500792: GPCR ligand binding
R-HSA-168256: Immune System
R-HSA-6783783: Interleukin-10 signaling
R-HSA-6785807: Interleukin-4 and 13 signaling
R-HSA-392499: Metabolism of proteins
R-HSA-381042: PERK regulates gene expression
R-HSA-375276: Peptide ligand-binding receptors
R-HSA-2559582: Senescence-Associated Secretory Phenotype (SASP)
R-HSA-162582: Signal Transduction
R-HSA-372790: Signaling by GPCR
R-HSA-449147: Signaling by Interleukins
R-HSA-381119: Unfolded Protein Response (UPR)

Summary
Symbol	CXCL8
Name	chemokine (C-X-C motif) ligand 8
Aliases	SCYB8; LUCT; LECT; MDNCF; TSG-1; IL-8; NAP-1; 3-10C; MONAP; AMCF-I; LYNAP; NAF; b-ENAP; K60; GCP1; neutrophi ......
Chromosomal Location	4q13-q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CXCL8 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining

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Literatures describing the relation between CXCL8 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
26719303	Colorectal Carcinoma	Promote immunity (infiltration)	Indeed, owing to IL-17 secretion, CRC-derived Th17 triggered the release of protumorigenic factors by tumour and tumour-associated stroma. However, on the other hand, they favoured recruitment of beneficial neutrophils through IL-8 secretion and, most importantly, they drove highly cytotoxic CCR5+CCR6+CD8+ T cells into tumour tissue, through CCL5 and CCL20 release.
19431148	Non-small-cell lung carcinoma	Promote immunity (T cell function)	Furthermore, all NSCLC cell lines secreted immunoreactive IL-8, albeit at different levels. IL-8 was as effective as TNFalpha in triggering ARG1 release and the 2 cytokines acted synergistically. Secreted ARG1 was biologically active and catabolized extracellular arginine.
19701890	Leukemia	Promote immunity	The TNF member LIGHT also known as TL4 or TNFSF14) can play a major role in cancer control via its two receptors; it induces tumor cell death through lymphotoxin-beta receptor (LT-betaR) and ligation to the herpes virus entry mediator (HVEM) amplifies the immune response. By studying the effect of LIGHT in the transcriptional profile of a lymphoid malignancy, we found that HVEM, but not LT-betaR, stimulation induces a significant increase in the expression of chemokine genes such as IL-8, and an unexpected upregulation of apoptotic genes. This had functional consequences, since LIGHT, or HVEM mAb, thus far known to costimulate T- and B-cell activation, induced chronic lymphocytic leukemia cell death. Many of the mediators involved were identified here, with an apoptotic pathway as demonstrated by caspases activation, decrease in mitochondrial membrane potential, upregulation of the pro-apoptotic protein Bax, but also a role of TRAIL. HVEM Moreover, HVEM induced endogenous TNF-alpha production and TNF-alpha enhanced HVEM-mediated cell death.
29486738	Breast Carcinoma; Melanoma	Inhibit immunity (T cell function)	IL-6, IL-8 and XIAP showed increased expressions in PTX-treated cells and this over-production effect was inhibited in TLR4-transient knockdown cells. Apoptotic cells were detected higher when PTX and CpdA were combined than PTX treatment alone. Isobologram exhibited the synergistic effect of CpdA and PTX. CpdA could significantly decrease expressions of IL-6, XIAP and IL-8, as well as excreted IL-8 levels together with reduced cancer viability after PTX treatment. The acquired TLR4-mediated PTX resistance in BCA and melanoma is explained partly by the paracrine effect of IL-6 and IL-8 released into the tumor microenvironment and over-production of anti-apoptotic protein, XIAP, in BCA cells and importantly CpdA could reduce this effect and sensitize PTX-induced apoptosis in a synergistic manner.
21480223	Bladder Carcinoma	Inhibit immunity	Both myeloid cell subsets from cancer patients were highly activated and produced substantial amounts of proinflammatory chemokines/cytokines including CCL2, CCL3, CCL4, G-CSF, IL-8 and IL-6. We demonstrate that these highly activated inflammatory myeloid cells represent a source of multiple chemokines/cytokines and may contribute to inflammation and immune dysfunction in bladder cancer.

Summary
Symbol	CXCL8
Name	chemokine (C-X-C motif) ligand 8
Aliases	SCYB8; LUCT; LECT; MDNCF; TSG-1; IL-8; NAP-1; 3-10C; MONAP; AMCF-I; LYNAP; NAF; b-ENAP; K60; GCP1; neutrophi ......
Chromosomal Location	4q13-q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

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Statistical results of CXCL8 in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	CXCL8
Name	chemokine (C-X-C motif) ligand 8
Aliases	SCYB8; LUCT; LECT; MDNCF; TSG-1; IL-8; NAP-1; 3-10C; MONAP; AMCF-I; LYNAP; NAF; b-ENAP; K60; GCP1; neutrophi ......
Chromosomal Location	4q13-q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

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Points in the above scatter plot represent the expression difference of CXCL8 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	-0.349	0.638
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.962	0.588
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.109	0.932
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	1
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	1
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	1
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.844	0.37
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-1.283	0.441
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.299	0.863
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.534	0.743
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	0.23	0.913
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.256	0.422

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of CXCL8 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	1.4	-1.4	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	1.7	-1.7	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	1

Summary
Symbol	CXCL8
Name	chemokine (C-X-C motif) ligand 8
Aliases	SCYB8; LUCT; LECT; MDNCF; TSG-1; IL-8; NAP-1; 3-10C; MONAP; AMCF-I; LYNAP; NAF; b-ENAP; K60; GCP1; neutrophi ......
Chromosomal Location	4q13-q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CXCL8. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	CXCL8
Name	chemokine (C-X-C motif) ligand 8
Aliases	SCYB8; LUCT; LECT; MDNCF; TSG-1; IL-8; NAP-1; 3-10C; MONAP; AMCF-I; LYNAP; NAF; b-ENAP; K60; GCP1; neutrophi ......
Chromosomal Location	4q13-q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CXCL8. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CXCL8. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CXCL8
Name	chemokine (C-X-C motif) ligand 8
Aliases	SCYB8; LUCT; LECT; MDNCF; TSG-1; IL-8; NAP-1; 3-10C; MONAP; AMCF-I; LYNAP; NAF; b-ENAP; K60; GCP1; neutrophi ......
Chromosomal Location	4q13-q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CXCL8. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	CXCL8
Name	chemokine (C-X-C motif) ligand 8
Aliases	SCYB8; LUCT; LECT; MDNCF; TSG-1; IL-8; NAP-1; 3-10C; MONAP; AMCF-I; LYNAP; NAF; b-ENAP; K60; GCP1; neutrophi ......
Chromosomal Location	4q13-q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CXCL8 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CXCL8
Name	chemokine (C-X-C motif) ligand 8
Aliases	SCYB8; LUCT; LECT; MDNCF; TSG-1; IL-8; NAP-1; 3-10C; MONAP; AMCF-I; LYNAP; NAF; b-ENAP; K60; GCP1; neutrophi ......
Chromosomal Location	4q13-q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CXCL8 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CXCL8
Name	chemokine (C-X-C motif) ligand 8
Aliases	SCYB8; LUCT; LECT; MDNCF; TSG-1; IL-8; NAP-1; 3-10C; MONAP; AMCF-I; LYNAP; NAF; b-ENAP; K60; GCP1; neutrophi ......
Chromosomal Location	4q13-q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CXCL8 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting CXCL8.

ID	Name	Drug Type	Targets	#Targets
DB05434	ABT-510	Small Molecule	CXCL8, FGF2, HGF, VEGFA	4
DB05484	MDX-018	Small Molecule	CXCL8	1
DB05855	Rivanicline	Small Molecule	CHRNB2, CXCL8	2
DB06083	Tapinarof	Small Molecule	CXCL8, IL12B, IL2, IL6	4

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